Introduction

Functional dyspepsia (FD) is one of the most common diseases of the digestive system, which comprises two subtypes, postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Acid suppression therapy has been recognized as the first-line treatment for H.pylori-negative FD patients. Potassium-competitive acid blocker (PCAB), a novel acid suppressant, has the characteristics of faster onset of effect and more stable acid suppression compared with traditional proton pump inhibitor (PPI). However, there has been no prospective study of PCAB for FD treatment.

Aims & Methods

This study was therefore conducted to investigate the efficacy and safety of PCAB in FD patients, and initially explore the effects of PCAB on gut microbiota. Patients diagnosed with FD were included prospectively. Eligible subjects were randomly assigned to the trial group and placebo group by 2:1, respectively, to receive Tegoprazan or placebo treatment with 50mg once a day for 2 weeks. 7-point global overall symptom scale (GOSS) was used to evaluate the relief of dyspepsia symptoms (primary endpoint) before the trial and at 1 and 2 weeks after randomization. Quality of life was assessed using the short form Nepean dyspepsia index (SFNDI). The generalized anxiety disorder-7 (GAD-7) and patient health questionnaire -9 (PHQ-9) were used to evaluate anxiety and depression, respectively. Stool samples were collected for 16SrRNA sequencing to evaluate gut microbiota alterations. Blood samples were collected to detect blood routine and blood biochemistry, and drug-related adverse events reported by subjects were collected to evaluate the safety of Tegoprazan.

Results

A total of 84 subjects were randomized, including 55 in the trial group and 29 in the placebo group. Among the subjects, 58.3% (49/84) were females, the median age was 51.00 (38.75, 55.00) years, and the mean BMI was 21.21 ± 3.06kg/m². For FD subtypes, EPS accounted for 44.0% (37/84), and no significant difference between the two groups was evident. In addition, there were no significant differences in the GOSS score, GAD-7 score and PHQ-9 score between the two groups at baseline. In the ITT analysis, the overall response rate was 25.5% (14/55) in the trial group and 17.2% (5/29) in the placebo group at 1 week, with no significant difference between the two groups (P =0.392). The 2-week response rate was 38.2% (21/55) in the trial group and 27.6% (8/29) in the placebo group, with no significant difference between the two groups (P =0.331). The results of PP analysis were consistent with ITT analysis. In the analysis of FD subtype, the response rate of EPS receiving Tegoprazan for 1 week was 45.8% (11/24), and that of the placebo group was 7.7% (1/13), with significant difference between the two groups (P =0.027).The response rate at 2 weeks of treatment with Tegoprazan was 50.0% (12/24), and the response rate after 2 weeks of placebo treatment was 15.4% (2/13), with no significant difference between the two groups (P =0.074). No significant difference was found between Tegoprazan and placebo on PDS (P > 0.05). In terms of gut microbiota, after 2 weeks of Tegoprazan treatment, the abundance of fecal genus streptococcus increased significantly (P < 0.001), especially streptococcus salivarius. There were no significant differences in the incidence of adverse events between the trial group and the placebo group (P > 0.05). No severe adverse events occurred in this study.

Conclusion

Tegoprazan is suitable for short course treatment of EPS. For patients requiring long-term treatment with Tegoprazan, the benefits of acid suppression should be weighed against the risk of intestinal microbiota dysbiosis. Tegoprazan had a similar safety profile to placebo.

Introduction

Subjectively reported sleep disturbances are common in IBS¹, as are psychological comorbidities². Whilst sleep and psychological disorders are clearly linked, it has been demonstrated that sleep disturbances amongst IBS patients appear to exist independently of psychological factors³, raising the potential for sleep as a novel intervention target in IBS. Developing our understanding of the role and associations of sleep within the disease experience of IBS patients could lead to better treatment.

Aims & Methods

We aimed to compare the characteristics of patients with IBS according to the quality of their sleep. Participants were recruited from the NIHR research register ContactME-IBS. We collected data for demographics, gastrointestinal symptoms^4,5,6, psychological health⁷, quality of life^8,9, and impact on work and daily activities¹⁰using validated questionnaires among adults with Rome IV IBS. We dichotomised the cohort according to whether they were good or poor sleepers, defined by a Pittsburgh sleep index score >5¹¹. We compared the characteristics of the two groups to explore significant associations.

Results

Of 341 respondents with Rome IV IBS, 287 (84.16%) were poor sleepers. A significantly higher proportion of poor sleepers had been diagnosed with IBS for 5 years or more (82.2% vs 66.7% p=0.009). A greater proportion of good sleepers had a university or postgraduate level of education (59.3% vs 41.1% p=0.014), though this did not meet our threshold for statistical significance. Poor sleepers had a significantly higher burden of severe somatisation, nearly fivefold that of good sleepers (60.3% vs 13% p=<0.001). Poor sleepers reported higher levels of anxiety and depression symptoms. Amongst the good sleepers, none had abnormal depression scores. Poor sleepers experienced greater impairment of their work activities, and were more adversely affected in their home and social activities (p=<0.001 across all analyses). Though not statistically significant, poor sleepers reported higher IBS symptom severity. There was no statistically significant difference between poor and good sleepers in relation to their IBS subtype.

Table 1. Characteristics of Individuals with Rome IV IBS according to the quality of their sleep.

Conclusion

Individuals with Rome IV IBS who report poor sleep have significantly higher levels of somatisation and psychological comorbidity and are more adversely affected in both their work and personal lives, compared with those who report good sleep. Our findings could support the potential of sleep as an intervention target in the management of IBS.

References

1. Tu Q et al. Neurogastroenterol Motil. 2017;29(3).
2. Zamani M et al. Alimentary pharmacology & therapeutics. 2019;50(2):132-43.
3. Koloski NA et al. Alimentary pharmacology & therapeutics. 2021;54(5):627-36.
4. Palsson OS et al. Gastroenterology. 2016:S0016-5085 (16) 00180.
5. Whitehead W et al. Rome III: The functional gastrointestinal disorders, 3rd editionVirginia: Degnon Associates Inc. 2006:835-53.
6. Labus JS et al. Alimentary pharmacology & therapeutics. 2004;20(1):89-97.
7. Spiller R et al. Alimentary pharmacology & therapeutics. 2010;32(6):811-20.
8. Patrick DL et al. Digestive diseases and sciences. 1998;43:400-11.
9. Drossman DA et al. Official journal of the American College of Gastroenterology| ACG. 2000;95(4):999-1007.
10. Reilly M et al. Alimentary pharmacology & therapeutics. 2004;20(4):459-67.
11. Buysse DJ et al. Psychiatry research. 1989;28(2):193-213

Introduction

Food related symptoms are frequently reported by patients with IBS and can occur within 30 minutes of a meal. The mechanisms underlying food-related symptoms likely involve local immunological reactions to food. To date, most research has focused on the distal GI tract and data on the proximal small intestine – the segment most exposed to food- is scarce.

Aims & Methods

Aim: To characterize the duodenal microenvironment, permeability and systemic inflammatory markers in patients with frequent food-related symptoms.
Methods: Cross-sectional study of a cohort of patients with IBS and age- and sex-matched healthy controls (HC). Symptoms were assessed using the Rome IV diagnostic questionnaire and daily symptoms were assessed daily using visual analog scales (reported as the mean of two weeks). Markers of systemic inflammation were assessed using Roche Cobas c502 (high-sensitivity C-reactive protein (hs-CRP)), Sysmex XN-9100 (white blood cell (WBC) count) and Thermo Fisher Phadia1000 (IgE and tryptase) on a Phadia 1000 platform. Small intestinal permeability was measured ex vivo in Ussing chambers, in vivo via the laculose/mannitol ratio in a 2-hour urine collection (LMR, 5g lactulose and 1g mannitol ) and by quantifying epithelial gaps using confocal laser endomicroscopy (CLE). Duodenal immune cell composition was quantified histologically and eosinophilic cationic peptide (ECP) and tryptase content were measured in mucosal lysates. Immune cell activity was assessed by quantifying the spontaneous release of tryptase and eosinophil-derived neurotoxin in biopsy supernatants. Assessed variables are presented in the table. Group-wise comparisons, correlation with daily symptoms and principal component analysis (PCA) were performed.

Results

Thirty-five patients with Rome IV IBS and 15 age- and sex-matched HC were included in this analysis. Patients with IBS had significantly higher tryptase content in the duodenal mucosa than HC (299 ng/mg total protein vs 143 ng/mg, p = 0.016) – none of the other variables were different between patients and HC. Based on the frequency of food-related pain, we subdivided patients with IBS into patients with frequent food-related pain (n = 22, overall ≥80% of abdominal pain episodes food-related) and patients with infrequent food-related pain. Using unsupervised PCA, patients with frequent and infrequent food-related symptoms did not cluster separately. There was no difference in duodenal eosinophil or mast cell counts between frequent and infrequent food-related pain. The proportion of patients with comorbid functional dyspepsia (FD) was not different between groups (45% vs 55%, p = 0.6). In the subgroup with frequent food-related symptoms, daily abdominal pain severity correlated significantly with LMR (r = 0.59, p = 0.02), hs-CRP (r = 0.69, p < 0.01) and WBC count (r = 0.55, p <0.01). In contrast, none of the duodenal variables correlated with pain severity.

Conclusion

The content of duodenal tryptase was significantly higher in patients with IBS than in HC. We found no differences in the duodenal micro-environment between patients with frequent and infrequent food-related symptoms. Among patients with IBS, the subgroup with the most frequent food-related symptoms showed significant correlations of daily pain severity and duration with hs-CRP, WBC and LMR, suggesting a possible pathophysiological role of systemic immune activation and small intestinal permeability. These preliminary findings warrant a larger-scale assessment.

Introduction

Gut microbiota in Crohn's disease (CD) exhibits considerable variability, with conflicting associations with disease severity and response to therapeutic intervention. We aimed to longitudinally investigate the dynamics of microbial composition in a cohort of patients with newly diagnosed, treatment-naïve Crohn's disease (ndCD) over a one-year period.

Aims & Methods

A prospective real-world study was conducted, enrolling patients with ndCD who were treatment-naïve. Treatment decisions were made by physicians with expertise in CD management. Key one-year clinical outcomes included corticosteroid-free clinical remission (CSFR) and biochemical remission (BR), defined as C-reactive protein levels <1mg/dL and fecal calprotectin levels <150ug/g. Paired stool samples were subjected to 16S rRNA gene sequencing (V4 region) at diagnosis and after one year, followed by analysis for microbial diversity and dysbiosis indices. A linear mixed-effect model was constructed to identify factors associated with microbial alterations and specific taxa driving these alterations, while controlling for confounding variables.

Results

Seventy-five patients completed the one-year follow-up (49.3% female, median age 27 years [IQR 22-38.5]); 45 (60%) received biologics (95.5% anti-tumor necrosis factor [TNF]). Rates of CSFR, BR, and combined CSFR-BR at one-year post-diagnosis were 64%, 56%, and 45.3%, respectively. Analysis of microbial composition revealed significant improvements in microbial indices among patients achieving all desired clinical outcomes, characterized by increased microbial diversity (Shannon index, p=0.004, p=0.002, p=0.004, respectively) and decreased dysbiosis (microbial dysbiosis index [MDI], p=0.003, p=0.04, p=0.01, respectively). Such improvements were not observed in patients failing to achieve CSFR, BR or combined CSFR-BR. Notably, patients treated with biologics, irrespective of outcome achievement, exhibited prominent shifts (improvement) in microbial composition (both indices p<0.001), whereas non-treated patients did not demonstrate significant changes (Shannon index, p=0.53; MDI, p=0.81). Furthermore, microbial composition at baseline was more disrupted among patients treated with biologics compared to non-treated patients (Shannon index, p=0.04; MDI, p=0.03). The linear mixed model analysis confirmed a positive association between biologics and favorable changes in microbial indices (Shannon index, p=0.02; MDI, p=0.04), identifying an increase in 20 gut commensal taxa (considered beneficial) and a decrease in Escherichia coli among the biologics-treated subgroup. Conversely, no taxa exhibited significant alterations in the non-biologics treated subgroup.

Conclusion

In a real-world cohort of patients with treatment-naïve ndCD, clinical improvement over one year was associated with improvement in microbial composition. Treatment with anti-TNF agents was associated with improvement in microbial composition irrespective of clinical outcomes. These findings suggest that microbial composition reflects inflammatory activity and may be positively and independently modified by anti-TNF treatment.